This project will carry out a program of computer simulation of energy metabolism in heart, brain, and liver, and of enzyme kinetics with emphasis on how enzymes fit into multi-enzyme systems and the improvement of enzyme assays in clinical pathology. Simulation techniques and software needed in the above work will be developed, improved, and distributed. Specific objectives include: 1. Cardiac Metabolism: To detemine metabolic control properties, mitochondrial-cytoplasmic interactions, etc. and explore the relationship between metabolic control and physiological behavior. 2. Liver Metabolism: To construct a working model of this area of metabolism in liver, and use it to study metabolic control, with emphasis on gluconeogenesis. 3. Brain Metabolism: To construct or extend past models of serotonin metabolism and of Krebs sycle-amino acid metabolism, and their application to problems such as compartmentation. 4. Clinical Pathology: To determine the best ways of assaying certain serum enzymes, starting with gamma-glutamyl tranferase, and hopefully to generalize this.